Impact: Optimizing clinical outcomes while minimizing unintended consequences for Veterans is the goal of the Veterans Health Administration (VHA) antibiotic stewardship program. Evidence indicates a strong link between recent antibiotic use and Clostridium difficile infection (CDI) which is an important cause of infectious disease death in the United States. It is estimated that CDI caused almost half a million infections in 2011. And, approximately 83,000 of patients who develop CDI experience at least one recurrence. On a broader level, antibiotic prescribing that is not concordant with guidelines is a critical factor in antibiotic resistance ? now being described as a worldwide public health crisis. Antibiotic-resistant infections affect healthcare costs, health outcomes and can lead to more toxic treatments. Background: Antibiotic stewardship efforts by VHA started years ago, culminating in a directive in January 2014 requiring all VA medical facilities to establish procedures to implement and maintain an antibiotic stewardship program. A recent Department of Veterans Affairs, Office of Inspector General ?Review of Antimicrobial Stewardship Programs in Veterans Health Administration Facilities? recommended that VA facilities track and generate clinical outcome reports on antibiotic use including in ambulatory settings. We know that at least 30% of antibiotics prescribed in ambulatory settings are not needed at all. Most of this unnecessary use is for acute respiratory conditions such as colds, bronchitis, sore throats caused by viruses, and even some sinus and ear infections. Total non- concordant antibiotic use, which includes selection of antibiotics, dosing and duration may approach 50% of all outpatient encounters. Although efforts are increasing to address this issue, the primary focus for research has been physician prescribing in pediatrics. Not much is known about nurse practitioner (NP) prescribing in adults and NP participation in antibiotic stewardship efforts. Our study will produce data, methods, and tools that have widespread relevance and portability, with the potential to reduce healthcare-associated infections including but not limited to CDI. Objectives: We hypothesize that understanding prescribing patterns of NPs and engaging NPs and Veterans in designing an antibiotic stewardship intervention will lead to an increase in guideline-concordant prescribing for non-specific upper respiratory infections in the ambulatory VA setting. We will use a systems approach to examine factors that hinder or help NPs in making decisions about prescribing an antibiotic?the Systems Engineering Initiative for Patient Safety (SEIPS) model. The specific aims are to describe NP prescribing patterns for non-specific upper respiratory illness, acute bronchitis and acute pharyngitis in the outpatient setting and to engage NPs and Veterans in the design of an antibiotic stewardship intervention. Methods: We will use the innovative SEIPS model of workflow and patient safety as the study framework. This model will guide interview and focus group questions. A minimum of 15 interviews of NPs will be conducted. Two focus groups will be conducted with patients with lived experience of a healthcare- associated infection and will include Veterans. These patient groups are already in place due to a Patient- Centered Outcomes Research Institute (PCORI) award. This is among the first research studies to systematically examine barriers and facilitators of guideline-concordant antibiotic prescribing by NPs. Our project is innovative in that it will employ the SEIPS framework to undertake a complete systems analysis of information gained from both NPs and Veteran patients; use complementary approaches to data collection; and consider not just prescribers, but also patients in the development of an intervention for ambulatory settings. Engaging Veteran patients in determining practical stewardship efforts will add to the fields of patient safety and infection control. If our goals are met, this project will lead to an investigator initiated research (IIR) proposal to fully develop and test (in multiple VA hospital settings) an intervention?informed by NP and Veteran stakeholders to increase guideline-concordant antibiotic prescribing in the VHA ambulatory setting.